No, nothing you do with the co-worker(s) locks you out of any part of the relationships with the girls. Anything that will permanently lock you out of any content with the girls will be marked with a text (something like "this will lock you out of the (M/D) path etc.").(...)I ignored almost everything about the coworker. (...)
I rejected her every time I could so I feel like I might have missed some content.
But I don't want to do it if it changes the relation with the girls permanently.
In fact, I really hate when games pull a "hey you completely missed this part of the game because you made a choice two hours back when you had no idea this was coming.", and there is also no branching content where, if you make choice A you will miss content B and if you make choice B you will miss content A.
Go ahead and explore, I put a lot of effort into those parts of the story and I'd hate for that effort to go to waste.